Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

Figure 1 Model of interaction between large envelope proteins and the sodium-taurocholate cotransporting polypeptide. A: Schematic diagram of hepatitis B virus envelope proteins: Small (S), Middle (M) and Large (L) envelope proteins. B: Representation of the interaction between the viral preS1 protein and its host receptor in hepatocytes, sodium-taurocholate cotransporting polypeptide (NTCP), modified from the model proposed by Urban[53]. The 2 domains analyzed in this study, the NTCP-interacting and virion morphogenesis (VM) domains, are indicated in the L protein. Numbering is based on the HBV genotype D consensus sequence. myr: Myristic acid; HBV: Hepatitis B virus.

Figure 2 Frequency of amino acid changes in each position in the two domains studied. In order to simplify the variations due to HBV genotype, the numeration of aa positions in both domains and their consensus sequences is presented according to genotype D (reference sequences obtained from GenBank, accession numbers provided in Supplementary table 1). Asterisks indicate positions where the wild-type aa varies according to HBV genotype. A: Schematic diagram where the two regions studied are represented: the sodium-taurocholate cotransporting polypeptide (NTCP)-interacting domain from residues 2 to 48 of the N-terminal end of preS1, and the virion morphogenesis (VM) domain from residues 92 to 108 of the C-terminal end of preS1 and the first 5 residues from the N-terminal end of preS2. B: Barplot representing the frequency of aa changes (above 1% of HBV quasispecies) within each HBV genotype in the NTCP interaction and virion morphogenesis domains (Specific aa changes are shown in Supplementary table 2).

Figure 3 Sequence logos showing the information content of amino acid positions from the sodium-taurocholate cotransporting polypeptide-interacting domain and the virion morphogenesis domain, in all the haplotypes obtained by next-generation sequencing. In order to simplify variations due to HBV genotype, the numeration of aa positions from both domains is presented according to genotype D: NTCP-interacting domain from residues 2 to 48 of the N-terminal end of preS1, and the virion morphogenesis domain from residues 92 to 108 of the C-terminal end of preS1 and first 5 residues from the N-terminal end of preS2. Positions where the wild-type aa varies according to HBV genotype have been highlighted in bold and red. aa: Amino acid; NTCP: Sodium-taurocholate cotransporting polypeptide.